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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/29218236/psmb5-plays-a-dual-role-in-cancer-development-and-immunosuppression
#1
Chih-Yang Wang, Chung-Yen Li, Hui-Ping Hsu, Chien-Yu Cho, Meng-Chi Yen, Tzu-Yang Weng, Wei-Ching Chen, Yu-Hsuan Hung, Kuo-Ting Lee, Jui-Hsiang Hung, Yi-Ling Chen, Ming-Derg Lai
Tumor progression and metastasis are dependent on the intrinsic properties of tumor cells and the influence of microenvironment including the immune system. It would be important to identify target drug that can inhibit cancer cell and activate immune cells. Proteasome β subunits (PSMB) family, one component of the ubiquitin-proteasome system, has been demonstrated to play an important role in tumor cells and immune cells. Therefore, we used a bioinformatics approach to examine the potential role of PSMB family...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29217193/regulation-of-inflammatory-gene-expression-in-macrophages-by-epithelial-stromal-interaction-1-epsti1
#2
Young-Hoon Kim, Jae-Rin Lee, Myong-Joon Hahn
Epithelial-stromal interaction 1 (EPSTI1) was first discovered as a gene induced in breast cancer epithelial cells by co-cultured stromal fibroblasts. There are many reports on the role of Epsti1 in cancer malignancy. Epsti1 is now well known in regulating cancer. Recently, the role of Epsti1 in the immune response has been reported; these reports suggest the role of Epsti1 in immune function, immune privilege, and autoimmune diseases. Furthermore, they show that Epsti1 is expressed in various types of immune cells...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#3
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29209558/development-and-clinical-application-of-anti-her2-monoclonal-and-bispecific-antibodies-for-cancer-treatment
#4
REVIEW
Shengnan Yu, Qian Liu, Xinwei Han, Shuang Qin, Weiheng Zhao, Anping Li, Kongming Wu
HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab, pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a classic drug for the treatment of HER2 positive metastatic breast cancer. The combined application of pertuzumab, trastuzumab and paclitaxel has been suggested as a standard therapy for HER2 positive advanced breast cancer. The resistance to anti-HER2 antibody has resulted in disease progression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29200846/improved-resection-and-prolonged-overall-survival-with-pd-1-irdye800cw-fluorescence-probe-guided-surgery-and-pd-1-adjuvant-immunotherapy-in-4t1-mouse-model
#5
Yang Du, Ting Sun, Xiaolong Liang, Yuan Li, Zhengyu Jin, Huadan Xue, Yihong Wan, Jie Tian
An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#6
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29189387/ex-vivo-expanded-natural-killer-cells-derived-from-long-term-cryopreserved-cord-blood-are-cytotoxic-against-primary-breast-cancer-cells
#7
Tina Nham, Sophie M Poznanski, Isabella Y Fan, Fatemeh Vahedi, Mira M Shenouda, Amanda J Lee, Marianne V Chew, Richard T Hogg, Dean A Lee, Ali A Ashkar
With over 600,000 units of umbilical cord blood (CB) stored on a global scale, it is important to elucidate the therapeutic abilities of this cryopreserved reservoir. In the advancing field of natural killer (NK) cell cancer immunotherapy, CB has proven to be a promising and noninvasive source of therapeutic NK cells. Although studies have proven the clinical efficacy of using long-term cryopreserved CB in the context of hematopoietic stem cell transplantations, little is known about its use for the ex vivo expansion of effector immune cells...
November 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29187401/delivering-type-i-interferon-to-dendritic-cells-empowers-tumor-eradication-and-immune-combination-treatments
#8
Anje Cauwels, Sandra Van Lint, Franciane Paul, Genevieve Garcin, Stefaan De Koker, Alexander Van Parys, Thomas Wueest, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Elke Rogge, Annick Verhee, Bart Vandekerckhove, Niko Kley, Gilles Uzé, Jan Tavernier
An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy cells and remain active in case of recurrence. Furthermore, it should preferably not rely on tumor-specific surface markers, as these are only available in a limited set of malignancies. Despite approval for treatment of various cancers, clinical application of cytokines is still impeded by their multiple toxic side effects. Type I interferon (IFN) has a long history in the treatment of cancer, but its multifaceted activity pattern and complex side effects prevent its clinical use...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29181007/interplay-between-natural-killer-cells-and-anti-her2-antibodies-perspectives-for-breast-cancer-immunotherapy
#9
REVIEW
Aura Muntasell, Mariona Cabo, Sonia Servitja, Ignasi Tusquets, María Martínez-García, Ana Rovira, Federico Rojo, Joan Albanell, Miguel López-Botet
Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29177095/targeting-immune-checkpoints-in-breast-cancer-an-update-of-early-results
#10
REVIEW
Cinzia Solinas, Andrea Gombos, Sofiya Latifyan, Martine Piccart-Gebhart, Marleen Kok, Laurence Buisseret
The immune tumour microenvironment has been shown to play a crucial role in the development and progression of cancer. Expression of gene signatures, reflecting immune activation, and the presence of tumour-infiltrating lymphocytes were associated with favourable outcomes in HER2-positive and triple-negative breast cancer. Recently, immunotherapy with immune checkpoint blockade induced long-lasting responses and improved survival in hard-to-treat malignancies (ie, melanoma and non-small cell lung cancer) and are changing treatment paradigms in a variety of neoplastic diseases...
2017: ESMO Open
https://www.readbyqxmd.com/read/29174433/novel-chimeric-parapoxvirus-cf189-as-an-oncolytic-immunotherapy-in-triple-negative-breast-cancer
#11
Audrey H Choi, Michael P O'Leary, Shyambabu Chaurasiya, Jianming Lu, Sang-In Kim, Yuman Fong, Nanhai G Chen
BACKGROUND: Triple-negative breast cancer is an aggressive subtype of breast cancer with high recurrence rate and poor prognosis. Here we describe a novel, genetically engineered parapoxvirus that efficiently kills triple-negative breast cancer. METHODS: A novel chimeric parapoxvirus (CF189) was generated via homologous recombination and identified through high-throughput screening. Cytotoxicity was assayed in vitro in 4 triple-negative breast cancer cell lines...
November 22, 2017: Surgery
https://www.readbyqxmd.com/read/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#12
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#13
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29151109/reporting-of-randomized-trials-in-common-cancers-in-the-lay-media
#14
Domen Ribnikar, Hadar Goldvaser, Alberto Ocana, Arnoud J Templeton, Bostjan Seruga, Eitan Amir
BACKGROUND: Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. METHODS: Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full...
November 18, 2017: Oncology
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#15
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147453/ctla-4-genetic-variants-rs11571317-and-rs3087243-role-in-susceptibility-and-progression-of-breast-cancer
#16
Maruthi Goske, V R Vinish Ramachander, Prasanna Latha Komaravalli, P Fazul Rahman, Chandrasekhar Rao, Parveen Jahan
Background: Dysfunctional regulation at immune checkpoints may lead to escape of the tumor cells and gives a scope to set in the unresolved Breast cancer (BC). The major anti-tumor retort is cell-mediated response which involves T lymphocytes. CTLA-4 (Cytotoxic T lymphocyte associated protein-4) with immune suppressive function and tolerance is associated with various autoimmune diseases and cancers including BC. The present study deals with CTLA-4 gene selected polymorphisms (rs11571317 C/T and rs3087243G/A) to explore their relation with breast cancer susceptibility and progression in BC patients...
October 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#17
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29145974/immunotherapy-for-triple-negative-breast-cancer-existing-challenges-and-exciting-prospects
#18
Hongyan Jia, Cristina I Truica, Bin Wang, Yanhong Wang, Xingcong Ren, Harold A Harvey, Jianxun Song, Jin-Ming Yang
Patients with breast tumors that do not express the estrogen receptor, the progesterone receptor, nor Her-2/neu are hence termed "triple negatives", and generally have a poor prognosis, with high rates of systemic recurrence and refractoriness to conventional therapy regardless of the choice of adjuvant treatment. Thus, more effective therapeutic options are sorely needed for triple-negative breast cancer (TNBC), which occurs in approximately 20% of diagnosed breast cancers. In recent years, exploiting intrinsic mechanisms of the host immune system to eradicate cancer cells has achieved impressive success, and the advances in immunotherapy have yielded potential new therapeutic strategies for the treatment of this devastating subtype of breast cancer...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29129789/dual-ph-responsive-multifunctional-nanoparticles-for-targeted-treatment-of-breast-cancer-by-combining-immunotherapy-and-chemotherapy
#19
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
November 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29129094/rational-combination-of-immunotherapy-for-triple-negative-breast-cancer-treatment
#20
Chia-Wei Li, Seung-Oe Lim, Jennifer L Hsu, Mien-Chie Hung
Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment...
October 2017: Chinese Clinical Oncology
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